A guide for the synthesis of key nucleoside scaffolds in drug discovery

Rajapaksha, Dinithi G.; Mondal, Subhojit; Wang, Jason W.; Meanwell, Michael W.

doi:10.1007/s00044-023-03096-w

Cited by 5 publications

(1 citation statement)

References 81 publications

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“…Many reviews dealing with nucleoside antivirals were published. Recent examples are accounts on fluorinated nucleosides [ 10 , 11 ], 4′-modified nucleosides [ 12 ], oxetanocin [ 13 , 14 ], marketed nucleosides [ 15 ], antiviral nucleosides and analogues [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], and the chemistry of nucleoside drugs [ 36 , 37 , 38 ]. However, these reviews predominantly consider chemical and structural aspects, with some discussion on the main nucleoside mechanisms of antiviral action [ 21 , 22 , 24 , 29 , 30 , 34 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Kamzeeva,

Aralov,

Alferova

et al. 2023

CIMB

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The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs.

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Section: Introductionmentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Kamzeeva,

Aralov,

Alferova

et al. 2023

CIMB

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Discovery and substrate specificity engineering of nucleotide halogenases

Ni,

Zhuang,

Shi

et al. 2024

Nat Commun

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C2′-halogenation has been recognized as an essential modification to enhance the drug-like properties of nucleotide analogs. The direct C2ʹ-halogenation of the nucleotide 2′-deoxyadenosine-5′-monophosphate (dAMP) has recently been achieved using the Fe(II)/α-ketoglutarate-dependent nucleotide halogenase AdaV. However, the limited substrate scope of this enzyme hampers its broader applications. In this study, we report two halogenases capable of halogenating 2ʹ-deoxyguanosine monophosphate (dGMP), thereby expanding the family of nucleotide halogenases. Computational studies reveal that nucleotide specificity is regulated by the binding pose of the phosphate group. Based on these findings, we successfully engineered the substrate specificity of these halogenases by mutating second-sphere residues. This work expands the toolbox of nucleotide halogenases and provides insights into the regulation mechanism of nucleotide specificity.

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Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

Pal,

Chandra,

Mondal

et al. 2023

Synlett

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After the isolation of two carbocyclic nucleosides, viz Neplanocin A and Aristeromycin, from natural sources, a revolution came into the scientific community to develop more versatile, therapeutically useful compounds. For this purpose, many new methods for the synthesis of the carbocyclic framework of nucleosides have been developed. The consequences of this effort led to the successful development of many marketable drugs. Due to the inherent benefits such as higher lipophilicity and metabolic stability associated with carbocyclic nucleosides, like resistance against glycosidic hydrolysis and modification of aromatic bases by cellular phosphorylases, make them popular for the development of drugs against cancer and different viruses. Classically, carbocyclic nucleosides of various ring sizes and configurations have been synthesized starting from a chiral pool such as ribose and glucose, etc., but recently, many other new asymmetric versions have also been developed. Herein, we present a recent development in the catalytic enantioselective synthesis of nucleoside analogues, including carbocyclic and other varieties. This review provides new insights into the future development of modified nucleosides.

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A guide for the synthesis of key nucleoside scaffolds in drug discovery

Cited by 5 publications

References 81 publications

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Discovery and substrate specificity engineering of nucleotide halogenases

Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

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